John D. Bartlett, Ph.D.
|Title||Associate Professor of Developmental Biology|
245 1st Street
Cambridge MA 02142
Available: 01/02/12, Expires: 09/01/15
Matrix metalloproteinases (MMPs) are a family of proteinases capable of cleaving virtually all extracellular matrix proteins including the extracellular domain of cadherins. MMPs play critical roles in reproduction, development, morphogenesis, wound healing, tissue repair, regeneration, remodeling, and cell movement. MMP20 is required for healthy dental enamel development. People and mice with homozygous MMP20 mutations have soft discolored enamel that may be hypoplastic and easily abrades from the dentin surface. Analyses of Mmp20 null mouse enamel reveals that the most abundant enamel matrix protein, amelogenin, is not processed properly, that the enamel has altered or non-existent rod patterns, and that the enamel organ has a deteriorating morphology as enamel development progresses. Strikingly, the Mmp20 null mouse enamel organ morphology is noticeably dysplastic during the maturation stage of development when MMP20 is no longer expressed (Fig. 3). We hypothesize that an inability to cleave cell-cell attachment proteins (cadherins) results in tight ameloblast cell-cell attachments that contribute to the maturation-stage enamel organ dysplasia. We also hypothesize that the tight ameloblast attachments preclude ameloblast movement necessary to form the decussating enamel rod pattern.
Interested students have two possibilities for participating in this line of research. First, the student may assist a Posdoctoral researcher with their ongoing experiments to define the role of MMP20 in mediating cell-cell attachment and in promoting cell movement necessary for proper dental enamel development. Second, the student may initiate a more independent project that would focus on identification of which classes of cadherins are expressed during the two major stages (secretory & maturation) of enamel development. This second project would be accomplished by means of the polymerase chain reaction (PCR) technique to allow the student maximum time flexibility for completion of the experiments. In other words, the student would not have to commit to any particular day to perform the experiments as would be the case if cell culture were part of the experimental protocol. No one has identified the classes of cadherins expressed in the enamel organ. Therefore, I expect this project to culminate in a peer-reviewed publication. To date, my laboratory has had four HSDM students as authors on four different peer-reviewed publications.
THE UNFOLDED PROTEIN RESPONSE IS INVOLVED IN DENTAL FLUOROSIS.
Summer, 06/16/08 - 08/02/08
Identifying Enamel Proteins in Bioengineered Teeth
Summer, 04/01/02 - 08/31/02
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